有關穿戴式血糖偵測器對預防與治療糖尿病之應用

王俊荃 1*、張祖榮 1、王鴻儒 2

1
高雄醫學大學
2
經濟部標準檢驗局

*通訊作者:[email protected]
摘要
無論第一型糖尿病、第二型糖尿病或妊娠糖尿病患者，經常需要測量血糖值（特別是第一型糖尿病患者，需要更頻繁
次數的血糖測試）。現今測試血糖值的方式，大多使用細針扎在指尖上，再擠出幾滴血液於感應試紙，並放入血糖測量機中檢測血
糖值。為減少糖尿病患使用不便，現行美商亞培糖尿病照護事業部(Abbott Diabetes Care)銷售 Freestyle libre
連續血糖監控儀，其傳感器則是將貼片黏於手臂，透過非接觸的手持機器，即可測量受檢者的血糖值，同時傳感器只要扎一次，即
可連續監控 14 天，在此期間毋需再扎針。惟其掃描儀與傳感器分離，再者掃描儀比較大，無法一直安裝在傳感器上。若能將掃描
儀整合鈕釦電池或無線充電電池、量測讀取設備及藍芽裝置，並縮小至傳感器 1-2 倍大，則可以在手機 APP 或 iWatch 接
受訊號，進而完成連續監測功能，俾利糖尿病患更方便且即時管理自己的血糖。

關鍵字：穿戴裝置、糖尿病預防與治療、智慧醫療

Application of wearable blood glucose detectors for the

prevention and treatment of diabetes

Jun-Quan Wang1*、Zu-Rong Chang1、Hung-Ju Wang2

1
Kaohsiung Medical University
2
Bureau of Standards, Metrology, and Inspection
* Corresponding Author:[email protected]

Abstract
No matter the type 1 diabetes, type 2 diabetes or gestational diabetes is, the
main problem to induce high risk for diabetic patients is blood glucose test (especially
to type 1 diabetic patients, who requires more frequent blood glucose tests than
others). At present, the most frequently used method of blood glucose test is patients
to take their blood sample from a vein in fingertip with a small needle, squeeze a few
drops of blood from patients, drop it on the test paper, and put it into the machine to
measure their blood glucose. In order to reduce the inconvenience of diabetic patients
to measure their blood glucose, the current Abbott Diabetes Care sells a FreeStyle
libre glucose monitoring system with sensors that attach patches to the arm and
measure the current blood glucose level with a handheld device (non-contact to the
sensor). As long as it is tied once, it can be continuously monitored patients’ blood
glucose for 14 days, during that time no further needles are needed. However, the
scanner is separated from the sensor, and the scanner is relatively large and cannot be
installed on the sensor with patients at all times. If the scanner can be integrated with
wireless rechargeable battery, measurement reading device and blue-tooth device into
the size to 1-2 times of the sensor, the diabetic patients can receive the signal in the
mobile APP or iWatch, to execute the continuous blood glucose monitoring system,
making diabetic patients more convenient to manage their blood glucose in time.

Keywords: wearable device, Diabetes prevention and treatment, and smart medical
device

Introduction
Diabetes is a chronic disease that occurs when the patients’ pancreas does
not produce enough insulin or their body cannot effectively use the produced insulin
which is a hormone that regulates blood glucose. Hyperglycemia or elevated blood
glucose is a common symptom of uncontrolled diabetes, which can cause serious
damage to patients’ many systems of the body over time, especially their nerves and
blood vessels [1]. According to report from World Health Organization, the population
of diabetic patients was 4.7% adults population in 1980 (around 108 million patients)
and increased to 8.5% adults population in 2014 (around 422 million patients, almost
quartile in 1980). The main reason to increase many diabetic patients is by risk factors
such as overweight or obesity [2]. The diabetes directly cause 1.6 million death in 2016
and high blood glucose directly cause 2.2 million death in 2012 [1]. The world
population of diabetes patients changes from 2017 to 2045 as shown in figure 1.
 Figure 1 The world population of diabetes patients change from 2017 to 2045
The cause of diabetes is that insulin can bring glucose from the blood into
the cells as energy for cell operations. There are two main factors that cause glucose
to reject to enter the cell and remain in the blood to induce high blood glucose as
follows [1]:
1. Insufficient insulin supply in the body: When the insulin supply in the body is
insufficient, glucose cannot be used by the cells through insulin, and stay in the
blood to induce the blood glucose higher than normal. Type 1 diabetes is caused
by insufficient secretion of insulin due to their pancreatic cells by their immune
system attacked [1A].
2. Insulin resistance: Insulin resistance is the abnormal use of insulin by cells.
Insulin cannot effectively metabolize glucose, causing glucose to stay in the
blood. The kidneys cannot be completely recovered glucose in the blood and
 remain glucose in the urine. Because the cells can't get enough energy, the
patients’ body thought that more insulin should be made to carry glucose. So, the
insulin is made non-stopping, but the main problem is that the cells have already
reacted to insulin inefficiently instead of lacking insulin. Then, their cells still
can't get enough energy from blood glucose, and finally the patients’ body will
lose weight quickly [1A].
Diabetes can be classified into four types, type 1 diabetes, type 2 diabetes,
gestational diabetes, or others, in the following:
1. Type 1 diabetes (as shown in figure 2, formerly known as insulin-dependent,
adolescent-onset or childhood-onset diabetes) stems from an abnormal
immune system in the patients’ body, and antibodies become indifferent to
the enemy to all organs. The antibodies start to attack pancreatic beta cells
(which make insulin) and induce the pancreas to fail to secrete insulin or only
a small amount of insulin secreted. The age of onset of type 1 diabetes is
usually below 30, probably due to the combination of genetic and
environmental factors. The number of patients is relatively small (about 5%
of the total patient population), patients with thin body, weight loss, polyuria,
often feel thirsty and other obvious symptoms, need long-term insulin
injection to control the disease [4].

Figure 2, Causes of diabetes type 1

2. Type 2 diabetes (as shown in figure 3, formerly known as non-insulin-
dependent or adult-onset diabetes) is more than 90% of patients with
diabetes. Patients often have no symptoms at the beginning of the disease.
The patients usually with long-term illness lead to physical changes, or
complications of diabetes when the patients were plagued by diabetes in
 shocked. Patients with type 2 diabetes may cause from hereditary reason, are
usually older than 40 years, and often have extrinsic features of obesity.
Patients with type 2 diabetes often suffer from adverse lifestyle effects or
decreased insulin secretion due to poor lifestyle habits (such as alcohol,
smoking, lack of exercise, heavy diet, etc.). In order to control the symptoms,
extra insulin injection or oral medication and changing lifestyle habits are
necessary by the patients’ body not effectively using insulin. The majority of
people with diabetes around the world are type 2 diabetic patients, mainly
due to overweight and lack of physical activity. Symptoms may be similar to
type 1 diabetic patients, but often the symptoms are not significant. As a
result, type 2 diabetes may be diagnosed after many years of onset, and
complications have occurred. Until recently, this type 2 diabetes was only
common in adults, and the current incidence has increased to children [4].

Figure 3, Causes of diabetes type 2

3. Gestational diabetes (as shown in figure 4) is hyperglycemia, a blood glucose
level higher than normal but below the diagnostic value of diabetes during
pregnancy. About 5% of women develop temporary diabetes symptoms
during pregnancy because of changes in the body's hormones that cause the
cells to block insulin. But the diabetes symptoms usually disappear after
delivery. It should be noted that if the mother suffers from gestational
diabetes during pregnancy but does not be treated properly, gestational
diabetes will indirectly cause the fetus to exhibit hyperglycemia and increase
the probability of congenital malformation, stillbirth, and giant infant disease.
Women with gestational diabetes have increased risk of complications during
pregnancy and childbirth. 15% to 50% of women who have had gestational
 diabetes will develop type 2 diabetes and their children are also at increased
risk of developing type 2 diabetes in the future. Gestational diabetes is
usually diagnosed through prenatal screening rather than after reporting
symptoms. If they have gestational diabetes during pregnancy, they should be
tested for blood glucose at postpartum periodically [4].

Figure 4, Causes of gestational diabetes

4. Others: There are a few cases of diabetes caused by pancreatic diseases,
endocrine diseases, drugs or other factors [4].
Meanwhile, according to the statistics of the American Diabetes Research
Institute, there were about 30.3 million people with diabetes in the United States in
2015 (about 9.4% of the total population), of which 23.1 million people with diabetes
have been diagnosed, and another 7.2 million people with diabetes have not yet been
diagnosed (about 23.8% of the total diabetes population) [5]. From the statistics of the
Health Promotion Administration, Ministry of Health and Welfare in Taiwan, there
are more than 2 million patients with diabetes in that country, and the patients are
increasing about 25,000 every year. That is the reason why diabetes is in the top ten
causes for the Chinese people death [6]. All types of diabetes can cause complications
in many parts of the body (as shown in figure 5), including heart attacks, strokes,
kidney failure, lower extremity amputations, vision loss and nerve damage, and may
increase the overall risk of premature death. Inadequate diabetes control during
pregnancy may increase the risk of fetal death and other complications or possible
complications [1].

Figure 5 Diabetes cause complications in the body

Diabetes Diagnosis
The hemoglobin A1c test (HbA1c), is a blood test for type 2 diabetes and
prediabetes. It measures the average blood glucose over the past 3 months. Doctors
can use HbA1c alone or in combination with other diabetes tests for diagnosis and use
HbA1c to understand and treat effectiveness for diabetes. This test is different from
the daily blood glucose test for diabetic patients [7]. The HbA1c value of normal
people should be less than 5.7%; the HbA1c value of latent diabetic patients is
between 5.7% and 6.4%, which is an important risk factor for type 2 diabetes, and
patients may need to be retested every year. The HbA1c value of patients with type 2
diabetes is greater than 6.5% and patients should have at least two HbA1c tests every
year [7]. Many European and American studies have pointed out that fasting plasma
glucose (FPG) is the first choice for screening prevention measures for primary
prevention of diabetes [8]. The oral glucose tolerance test (OGTT) can be used to
diagnose deterministic diabetes. In the current European guideline, it is recommended
that all populations with fasting plasma glucose at 6.1-6.9 mmol/l (110-125 mg/ml)
undergo an oral glucose tolerance test to determine the diagnosis of diabetes. The
fasting plasma glucose continued to track fasting plasma glucose values after 12
months in the 5.0-6.0 mmol/l (90-109 mg/ml) population. For the diagnosis of
diabetes, it is necessary to repeat the test data twice or more to be the basis of
diagnosis [9]. Earlier internationally famous diabetes research began in the 1984
Diabetes Control and Complications Trial (DCCT) and the United Kingdom
Prospective Diabetes Study (UKPDS). There are clinical studies of the importance of
HbA1c in patients with diabetes. Since the publication of the DCCT study in 1993,
the international standardization problem of HbA1c testing has become an important
issue of concern for scientists and clinicians [10]. The National Glycohemoglobin
Standardization Program (NGSP) in the United States uses high performance liquid
chromatography (HPLC) as a reference method in DCCT research. It is the most
widely used standardization program in the world, and it will pass to the manufacturer
or clinical laboratory. The test results are compared with the results of the NGSP
reference laboratory to achieve consistency of all test results. NGSP's certification of
various testing methods in the laboratory plays an important role in promoting the
improvement of methodology, significantly reducing the variation of laboratory
testing and improving the accuracy of testing [10].
Due to the lack of original or primary standards, and in order to overcome
this shortcoming and meet the requirements of the European Union for in vitro
diagnostic medical devices, the International Federation of Clinical Chemistry and
Laboratory Medicine (IFCC) sets HbA1c standardization working group to establish a
reference detection system for quantifiable traceability in 1994. Its reference
laboratory network and reference method which not be accepted by the government
had been established until 2001. In August 2010, the International Consensus for
Standardization of Glycosylated Hemoglobin A1c Testing clearly stated that the IFCC
detection reference system is the only one legally valid reference system in the world.
This requires that all levels of laboratories must be traced the detection system to the
IFCC reference system. The standard material used in the IFCC reference system is a
purified β-chain N-terminal proline that stably binds glycosylated hemoglobin
molecules (IFCC 466, 467). The reference method is HPLC tandem mass
spectrometry or HPLC tandem capillary electrophoresis. Therefore, for clinical
laboratories, the detection system used must be traceable to the IFCC reference
method, and the analytical performance must meet the NGSP certification standard,
so as to ensure the accuracy of the test results [10]. On October 15, 2018, Taiwan Food
and Drug Administration has announced Home Blood Glucose Monitoring System
Technical Benchmark to require the glucose test system for measuring quantitative
glucose in blood and other body fluids to comply with international standards ISO
15197 In vitro diagnostic test systems -- Requirements for blood-glucose monitoring
systems for self-testing in managing diabetes mellitus. This amount of quantitative
glucose in blood and other body fluids is measured for the diagnosis and treatment of
various carbohydrate metabolic diseases, including diabetes (Diabetes mellitus),
Hypoglycemia and Hyperglycemia, and Pancreatic islet cell carcinoma [11].

Diabetes Prevention and Treatment

The definition of prediabetes refers to a metabolic abnormal state between
normal blood glucose and diabetes. According to the American Diabetes Association's
explanation, it is necessary to take blood glucose tests 8 hours after an empty stomach
overnight. The blood glucose between 110 mg/dl and 126 mg/dl causes an impaired
fasting glucose (IFG) and after an empty stomach for 8 hours to receive oral glucose
tolerance check for two hours of blood glucose, between 140mg / dl and 200mg / dl
form impaired glucose tolerance (IGT). It is diabetes when fasting blood glucose
levels over 126 mg / dl and glucose tolerance test the blood glucose level reaches 200
mg/dl or more [11]. Epidemiological studies at home and abroad have found that these
prediabetes cases have a 5-10% chance of turning into diabetes each year. According
to the US Diabetes Prevention Program within every 3 years of research, there is 11%
of prediabetes converted into diabetes annually. The domestic study of glucose-
resistance in Kinmen has 8.8% of prediabetes conversion to diabetes annually [12].
Studies have found that the incubation period of prediabetes can be as long
as 7 to 10 years, and many people with diabetes have been suffering from diabetes for
many years before they have a definite diagnosis. Therefore, for the treatment of
diabetes, early detection and timely control are also very important. According to
Finnish Diabetes Prevention Trial, Diabetes Prevention Program, Study to Prevent
Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM), etc., lifestyle changes,
such as diet control, regular exercise, weight loss, etc., can reduce the chance of
prediabetes becoming diabetes. In particular, the Diabetes Prevention Program in the
United States found that moderate exercise (such as 30 minutes a day, at least five
days a week, up to 150 minutes per week) plus 5-10% of the original weight loss has
chance of reducing prediabetes into diabetes is up to 58%. Some drugs such as
metformin, Acarbose, etc. also have some chances to reduce the conversion of
prediabetes into diabetes, but the effect is slightly lower than the change of lifestyle
[12]
.
The most important clinical manifestation of diabetes is hyperglycemia. If
the diabetic patients can control their blood glucose at normal or near normal blood
glucose level, patients can significantly reduce the morbidity and mortality of
ketoacidosis or hyperglycemia, high osmolality, non-ketone body coma, and improve
clinical symptoms (such as itching, polyuria, thirst, fatigue, blurred vision, etc.), delay
or even prevent chronic complications (for example, retinopathy, nephropathy,
neuropathy) and improve dyslipidemia to help prevent atherosclerosis [13]. How to
control the patient's blood glucose to be normal or close to normal, a complete
diabetes comprehensive care plan that requires professional medical staffs and the
patients to work together, including patients self-monitoring, nutritional therapy,
regular exercise, medication, prevention and treatment of hypoglycemia and other
acute and chronic complications, continuing education and enhancement, and regular
assessment of treatment to achieve these outcomes and goals [12].
The goal of diabetes medical nutrition therapy is to maintain blood glucose
in the normal range (to prevent or reduce the risk of diabetes-related complications),
to maintain blood fat in the normal range (to reduce the risk of macro vascular
disease), to control blood pressure (to reduce the risk of vascular disease). This
diabetes medical nutrition therapy also wants to achieve and maintain optimal
metabolic control, prevent and treat chronic complications of diabetes, and correct the
nutritional intake and lifestyle (to prevent and treat obesity, dyslipidemia,
cardiovascular disease, hypertension, and renal disease). Healthy food and exercise to
improve health and to meet individual nutritional needs should be considered the
personal cultural background and lifestyle, and respect individual expectations and
willingness to change [14]. Treatment for Type 2 diabetes includes nutrition, exercise,
medicine, and education. Nutrition and exercise are the basic steps, and those with
higher blood glucose are treated differently depending on the condition; drug
treatment includes oral anti-diabetic drugs (OAD) and insulin injection. Severe
symptoms or fasting blood glucose often exceed 250~300 mg / ml, patients need to
use insulin injection immediately. Otherwise, patients can try oral hypoglycemic
drugs to monitor the effectiveness [15].
The causes of all types of diabetes come from genetics and primary
prevention of diabetes from lower risk of developing diabetes. Once symbol of
prediabetes found, people should take necessary action to prevent or delay diabetes
under high risk condition. Then, diabetes patients should take necessary action to
management and prevention to their complication as shown in figure 6.
 Figure 6 Diabetes prevention and treatment
Generally defined hyperglycemia means that the fasting blood glucose level
of diabetic patients reaches 130 mg/dl and the blood glucose level after meals reaches
200 mg/dl or more. When the blood glucose level exceeds 600 mg/dl, diabetic
patients is easy to cause high osmotic hyperglycemia (HHS, usually occurred in
patients with type 2 diabetes) and diabetic ketoacidosis (DHA, usually occurred in
patients with type 1 diabetes). High osmotic hyperglycemia is caused by high osmotic
pressure, and dehydration leads to unconsciousness. Diabetic ketoacidosis is caused
by insufficient insulin in the body. The body begins to break down fat as heat,
producing ketone bodies, causing nausea and vomiting and breathing with fruity
aroma, and then headache coma. If patients have hyperglycemia in diabetic patients,
but patients can still eat and have no other physical condition, it is recommended to
take a break and relieve some boiled water. If patients are unable to handle the
emergency, patients should seek medical attention immediately and closely monitor
patients’ blood glucose and situation of body fluid electrolytes [16].
Healthy people's blood glucose will not be lower than 70 mg / dl, because
many organs and cells in the body need enough glucose to maintain the operation.
Once the body detects low blood glucose, it will start liver glycogen decomposition or
gluconeogenesis, resulting in glucose into blood. When blood glucose is lower than
70 mg/dl, diabetic patients may develop autonomic nervous symptoms (such as
trembling, sweating, rapid heartbeat, difficulty breathing, etc.), which may lead to
central nervous system lack of glucose supply symptoms (for example, dizziness,
blurred vision etc.), if the patients’ blood glucose is between 45 and 70 mg/dl, you can
add 15 grams of sugar at a time. If the patients’ blood glucose is lower than 45 mg/dl,
you need to add 30 grams of sugar instead. If patients finish the sugar every 15
minutes, and their blood glucose is still under 70 mg/dl, add 15 grams of sugar until
the blood glucose returns to 70 mg/dl. Some people with diabetes have a rapid decline
in blood glucose (for example, 350 mg / dl dropping to 220 mg / dl), because the body
cannot adapt to the illusion of rapid changes in blood glucose, called "pseudo-
hypoglycemia", it is recommended that patients sit and take a break, And drink some
boiled water, the symptoms will be relieved [17].

Blood Glucose Monitoring

The "diabetes control and complication test" in the United States tells us that
normalization of blood glucose is the only way to reduce micro-vascular
complications (such as, retinopathy and nephropathy, even neuropathy). The UK's
"United Kingdom Prospective Diabetes Study" shows that to control of blood glucose
is important for macro-vascular disease (including myocardial infarction, stroke,
lower extremity vascular occlusion, etc.) and to control blood pressure seems to be
more important. The Finnish "East-West Research" clearly states that when suffering
from diabetes, the incidence of myocardial infarction is 2-4 times higher than that
without diabetes. So the United States National Cholesterol Education Program
decided to treat people with diabetes as people with myocardial infarction. It is
recommended that people with diabetes actively control cholesterol concentrations
compared with patients with myocardial infarction [17]. The American Diabetes
Association recommends patients control their blood glucose within 80-120 mg/ml
before three meals, but in order to avoid low blood glucose in the middle of the night,
their blood glucose before bedtime is controlled within 100-140 mg/ml. Traditional
personal portable blood glucose machines require blood drops (0.5-3 μl). They use a
fine needle to pin on the fingertips, squeeze a few drops of blood, drop blood on the
induction test paper, and put test paper into the machine that measures blood glucose
before measuring. Because it hurts patients and no one teaches the patients how to
adjust the dose or food of the drug based on the blood glucose level, this
comprehensive care plan cannot be continued with the patients losing the motivation
and not having blood glucose test [18].
Since 1980, there are a lot of papers to discuss needle-type glucose sensor. In
1982, Professor Motoaki Shichiri has tested in pancreatectomised dogs with the
perfect control of blood glucose device for up to 7 days[19]. Then in 1984, Professor
Peter Ulrich Abel has developed a modification of a Clark-type glucose electrode for
implantation and for connection to a glucose-controlled insulin infusion system as a
long-term functioning implantable instrument [20]. After that in 1985, Professor John
C. Pickup has found chemical biosensor recognizes the analyze of interest through
relatively specific reactions such as that of antigen with antibody or sugar with lectin
[21]
In 1986, Professor Claremont DJ has used entrapped 1,1'-dimethylferrocene to
mediate electron transfer between immobilised glucose oxidase and a carbon base
electrode in pig as pilot technology of an implantable glucose sensor for use in
diabetic man [22]. Then in 1988, Professor David R Matthews has used an
amperometric glucose-measuring 25 gauge (0.5 mm diameter) needle-type sensor to
get stable glucose concentration over 6.0 h in rats and 4.5 h in man[23]. After that in
1988, Professor John C. Pickup has used 1,1’-dimethylferrocene acting as the redox
shuttle between immobilized glucose oxidase and a platinum base electrode to reduce
the delay in the hypoglycaemic nadir in 4 min and expand the detection for
hypoglycaemia[24]. Right now, the technology of needle-type glucose sensor is
matured and the US Food and Drug Administration (FDA) approved a continuous
blood glucose monitor, Freestyle Libre continuous blood glucose monitoring, and can
be used by the general public at home and sold by Abbott Diabetes Care in September
2017 [25]. The sensor is a patch on the arm and can measure blood glucose for 14
consecutive days in a non-contact handheld machine (continuous monitoring of the
blood glucose system). At the same time, the sensor only needs to be tied once, the
blood glucose measuring device is inserted under the skin, and the glucose
concentration in the tissue fluid is measured, and the monitoring can be continuously
monitored for 14 days, without any needle needed. However, the scanner is separated
from the sensor, and the scanner is relatively large and cannot be installed on the
sensor at all times.
Existing MiaoMiao's Freestyle Libre reader integrates the wireless
rechargeable battery, measurement reading device and blue-tooth device. Each time
the reading meter can be used 2 weeks, and the size of reading instrument is reduced
to 1-2 times of the sensor. And the reading instrument itself has a waterproof function,
which can read the blood glucose value every 5 minutes, patients can receive the
signal in the mobile APP or iWatch, and then complete the continuous monitoring
function to make it easier for diabetic patients to manage their blood glucose instantly
[26]
.

Application
Continuous blood glucose monitoring equipment has not only to comply
with requirements of international standards, ISO 13485 Medical Devices - Quality
Management Systems, but also use the mobile APP or iWatch wireless transmission
to remote calibration for the measurement results met the requirements of
international standards, ISO 15197 In vitro diagnostic test systems -- Requirements
for blood-glucose monitoring systems for self-testing in managing diabetes mellitus.
According to related study, Freestyle Libre continuous blood glucose monitoring had
met the requirements of ISO 15197 but without indication of Hypoglycemia and pre-
meal or after meal [27]. In order to let diabetic patients knowing that the effects of their
diet and quantity to their blood glucose, and adjust their healthy diet. At the same
moment, it can be further set by mobile APP or iWatch to control their blood glucose
near the normal range be insulin injection or oral medication in time and avoid the
occurrence of hyperglycemia and hypoglycemia.
Right now, the FREESTYLE LIBRE STARTER PACK with two sensors
and one reader are sold at $159.95 pounds (about $194.15 USD) on Freestyle Libre
official website [28]. Meanwhile, only one MIAOMIAO SMART READER is sold at
$139USD [26]. If we can domestic manufacturing with proper quality control and
calibration to put two MIAOMIAO SMART READERs and six FREESTYLE LIBRE
sensors in one package with lower cost $250 USD (two readers cost $100 USD and
six sensors cost $150 USD) for 3 month term or cost $700 USD (two readers cost
$100 USD and twenty four sensors cost $600 USD) for one year term under health
insurance program as shown in figure 7. To whose blood glucose in prediabetes
(about U.S. 7.2 million patients in 2015) uses this 3 month term continuous blood
glucose monitoring system. We can cost only 1.8 billion to prevent those 7.2 million
pre-diabetic patients from diabetic patients in the future. These two 3 month term
continuous blood glucose monitoring systems can also be used to gestational diabetes
in pregnancy and after delivery respectively. And to whose blood glucose in diabetes
(about U.S. 23.1 million patients in 2015) uses this continuous blood glucose
monitoring system. We can cost 16.17 billion annually to prevent those 23.1 million
diabetic patients (including type 1 diabetic patients and type 2 diabetic patients) from
the morbidity and mortality of ketoacidosis or hyperglycemia, high osmolality, non-
ketone body coma, and improve clinical symptoms, delay or even prevent chronic
complications and improve dyslipidemia to help prevent atherosclerosis. Furthermore,
the population of the United States is just above 330million [29]. If we want to every
citizen of the United States has continuous blood glucose monitoring system to check
their blood glucose in time each year, we need the budget about 231billion(330
million*700) USD annually. If we take the first quarter of this budget (57.75 billion
USD) as the royal fee to Abbott and MiaoMiao and the second quarter (57.75 billion
USD) of this budget as medical service fee for doctor and the one third of this budget
(77 billion USD) as manufacturing cost, the rest of one sixth of the this budget (38.5
billion USD) as the communication fee for High-speed, low latency broadband
internet in 5G、6G or starlink. Then we can consider how to manufacturing 330
million of 1 year term package in domestic manufacturing plant annually. Meanwhile,
we can take 12 consumers into a package to share communication fee if we use
starlink with $99 per month and a $499 upfront cost to order the Starlink Kit for 5
year depression[30] . Therefore, the diabetes may be the first controllable chronic
disease in this century.

Figure 7 Domestic manufacturing to reduce cost

Conclusion
This paper discussed solution on FREESTYLE LIBRE and MiaoMiao 2 to
demonstrate the combination of continuous blood glucose monitoring system with
blood glucose detector without any needle needed and continuous data reader in every
two weeks. The cost benefit analysis in above is a basic concept to provide
application of affordable wearable device to diabetes patients without any commercial
purpose. According related research, it is crucial in enabling research in
thermoregulation to measure and quantify body temperature accurately[31].To similar
concept of this study, we can use non-touch temporal artery thermometers[32] to
measure body temperature from subcutaneous tissue every 5 minute. If there is any
fever symptom continuous found in 30 minutes, we can first alarm the patient and
people around him/her to wear the medical face mask to prevent from virus infection
at that moment. Then, the patient should be taken the reverse transcription polymerase
chain reaction (rRT-PCR) test for the qualitative detection of nucleic acid from
SARS-CoV-2. Once the test result is positive, we can give the patient with proper
treatment and use the patient route map to find possible infection area to disinfect and
sterilize that area. Meanwhile, the blood oxygen concentration is a crucial index to
maintain patient life. If your oxygen level is below 90%, get immediate medical help.
If your oxygen level is 90% or more but less than 94%, contact your health care
provider or seek hospital care. If your oxygen is above 94%, continue to monitor your
oxygen level three times a day[33]. It will be helped to reduce the infection and
mortality of SARS-CoV-2 in the future also.
 Reference
1. World Health Organization website, Diabetes, 30 October 2018<
https://www.who.int/news-room/fact-sheets/detail/diabetes>.
1A. Diabetes.co.uk - the global diabetes community website, Insulin Resistance <
https://www.diabetes.co.uk/insulin-resistance.html >
2. World Health Organization website, 2016, Global Report on Diabetes.。
3. The National Institute of Diabetes and Digestive and Kidney Diseases website,
Symptoms & Causes of Diabetes < https://www.niddk.nih.gov/health-
information/diabetes/overview/symptoms-causes>.
4. American Diabetes Association website, Diabetes Symptoms <
https://www.diabetes.org/diabetes/type-1/symptoms>.
5. Prevalence of Diagnosed Diabetes, United States Centers for Disease Control and
Prevention (CDC), National Diabetes Statistics Report, 2020, P4
<https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-
report.pdf>.
6. Institute for Health Metrics and Evaluation website, China <
http://www.healthdata.org/china>.
7. United States National Library of Medicine website, A1C <
https://medlineplus.gov/a1c.html>.
8. Gerstein, H (2001), Fasting Versus Postload Glucose Levels, Why the
controversy? , Diabetes Care; 24(11): 1855-1857.
9. Diabetes.co.uk - the global diabetes community website, Blood Sugar Level
Ranges, < https://www.diabetes.co.uk/diabetes_care/blood-sugar-level-
ranges.html>.
10. NGSP website, 1 Minutes of the NGSP/IFCC Manufacturer Forum <
http://www.ngsp.org/docs/MF2018.pdf>.
11. Michael J. Thompson, MD and John P. Mordes, MD (2015), Hypoglycemia in
Pancreatic Disease, Pancreapedia <
https://www.pancreapedia.org/sites/default/files/DOI%20Ver%203.%20Thompson
%20and%20Mordes%20Pancreapedia%20Hypoglycemia%20Chapt%20Apr
%204.pdf>.
12. Adam G. Tabák, MD, PhD, Christian Herder, PhD, Wolfgang Rathmann, MSPH,
Eric J. Brunner, PhD, FFPH, and Mika Kivimäki, PhD, Professor (2012),
Prediabetes: A high-risk state for developing diabetes, Lancet. 379(9833): 2279–
2290.
13. National Center for Biotechnology Information website, Feingold KR, Anawalt B,
 Boyce A, et al., editors.South Dartmouth (MA): MDText.com, Inc.; 2000-
Diabetes and Dyslipidemia < https://www.ncbi.nlm.nih.gov/>.
14. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report <
https://care.diabetesjournals.org/content/42/5/731>.
15. Reinhard G. Bretzel, MD, PHD, Michael Eckhard, MD, Wolfgang Landgraf,
PHD, David R. Owens, MD, FRCP and Thomas Linn, MD, PHD (2009),
Initiating Insulin Therapy in Type 2 Diabetic Patients Failing on Oral
Hypoglycemic Agents Diabetes Care; 32(suppl 2): S260-S265.
16. WebMD website, High blood sugar and diabetes
<https://www.webmd.com/diabetes/guide/diabetes-hyperglycemia>.
17. WebMD website, Health2Sync website, Hypoglycemia: When Your Blood Sugar
Gets Too Low < https://www.webmd.com/diabetes/guide/diabetes-
hypoglycemia>.
18. Arun Chaudhury, Chitharanjan Duvoor, Vijaya Sena Reddy Dendi, Shashank
Kraleti, Aditya Chada, Rahul Ravilla, Asween Marco, Nawal Singh Shekhawat,
Maria Theresa Montales, Kevin Kuriakose, Appalanaidu Sasapu, Alexandria
Beebe, Naveen Patil, Chaitanya K. Musham, Govinda Prasad Lohani, and
Wasique Mirza (2017), Clinical Review of Antidiabetic Drugs: Implications for
Type 2 Diabetes Mellitus Management, National Center for Biotechnology
Information, U.S. National Library of Medicine Website <
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256065/>.
19. Shichiri M, Yamasaki Y, Kawamori R, Abe H (1982) Wearable artificial pancreas
with needle type glucose sensor. Lancet II: 1129–1131.
20. Abel P, Müller A, Fischer U (1984) Experience with an implantable glucose
sensor as a prerequisite of an artificial beta cell. Biochem Biomed Acta 43: 577–
588.
21. Pickup JC (1985) Biosensors: a clinical perspective. Lancet II: 817–820.
22. Claremont DJ, Sambrook IE, Penton C, Pickup JC (1986) Subcutaneous
implantation of a ferrocene-mediated glucose sensor in pigs. Diabetologia 29:
817–821.
23. Matthews DR, Bown E, Beck TW et al. (1987) An amperometric needle-type
glucose sensor tested in rats and man. Diabetic Med 5: 248–252.
24. Pickup JC, Shaw GW, Claremont DJ (1989) In vivo molecular sensing in diabetes
mellitus: an implantable glucose sensor with direct electron transfer. Diabetologia
32: 213–217.
25. Abbott Laboratories website, Introducing the FreeStyle Libre 14 day system! <
https://www.freestylelibre.us/system-overview/freestyle-14-day.html>.
26. Diabetes life hacks website, My experience with the MiaoMiao Freestyle Libre
 Transmitter < https://diabeteslifehacks.com/en/ >.
27. Li-Chi Huang, Yu-Hsin Chen, Chih-Chung Lee, and Ching-Ling Lin, DOI:
10.6314/JIMT.2016.27(5).03, Confounding Factors for Accuracy – Lesson from
the Latest International Standard of Self-monitoring Blood Glucose System
<http://www.tsim.org.tw/journal/jour27-5/03.PDF>.
28. Freestyle Libre official website, FREESTYLE LIBRE STARTER PACK <
https://www.freestylelibre.co.uk/libre/products/starter-pack.html>.
29. United States Census Bureau website, U.S. and World Population Clock<
https://www.census.gov/popclock/ >
30. SpaceX prices Starlink satellite internet service at $99 per month, according to e-
mail<https://www.cnbc.com/2020/10/27/spacex-starlink-service-priced-at-99-a-
month-public-beta-test-begins.html>
31. Chin Leong Lim, Chris Byrne, Jason KW Lee, Human, Thermoregulation and
Measurement of Body Temperature in Exercise and Clinical Settings, Annals,
Academy of Medicine, Singapore, April 2008, Vol. 37 No. 4
<https://www.annals.edu.sg/pdf/37VolNo4Apr2008/V37N4p347.pdf>
32. Davie A, Amoore J (2010) Best practice in the measurement of body temperature.
Nursing Standard. 24, 42, 42-49 Best practice in the measurement of body
temperature<https://pdfs.semanticscholar.org/d489/4b175de1b2c27b258b146f86b
1b77f614004.pdf>
33. Managing COVID-19 at Home: Checking Blood Oxygen Levels, <
https://reliefweb.int/report/world/managing-covid-19-home-checking-blood-
oxygen-levels>